The goal of this research program is to define mechanisms that promote mammalian oogenesis in vivo using model systems for oocyte development in vitro. Mouse oocytes, including those from primordial follicles, can grow in vitro and acquire competence to undergo embryogenesis. However, their growth and development in vitro does not produce oocytes equivalent to those grown in vivo. Experiments will (1) address the nature of defects in oocytes grown in vitro and their consequences to subsequent embryogenesis and long-term health of offspring and (2) explore the communication between oocytes and granulosa cells and its impact on oocyte development.
Specific Aim 1 will determine whether defects in oocyte development in vitro are due to failures in nuclear and/or cytoplasmic processes. Female pronuclei, male pronuclei, or both pronuclei will be microsurgically exchanged between fertilized eggs derived from oocytes grown in vitro and in vivo. Developmental potential and epigenetic programming in nuclear transplant embryos will be assessed.
Specific Aim 2 will determine whether conditions of oocyte development in vitro affect post-implantation development and long-term health of offspring. Genetically marked embryos derived from in vitro-grown and in vivo-grown oocytes will be transferred together to recipient mothers. Offspring will undergo a battery of health-evaluation protocols such as gross assessment, blood chemistry, hematology, and histopathological evaluation. This will be the first systematic assessment of both short-and long-term health effects of oocyte development in vitro.
Specific Aim 3 tests the hypothesis that a communication loop between oocytes and oocyte-associated granulosa-cells (OAGCs) regulates the differentiation of OAGCs in ways that promote normal oocyte development. Paracrine factors secreted by oocytes affect the differentiation and function of OAGCs in cultured oocyte-granulosa cell complexes will be either augmented or perturbed by co-culture of complexes with denuded oocytes that either match or mismatch the developmental stage of the oocyte resident in the complex. Effects on growth, maturation, fertilization, epigenetic programming, and developmental competence of granulosa cell-enclosed oocytes will be determined. Taken together, these studies will advance understanding of the mechanisms of oogenesis, improve conditions for oocyte development in vitro, and define the consequences of suboptimal conditions during oogenesis.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Tasca, Richard J
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Jackson Laboratory
Bar Harbor
United States
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Wigglesworth, Karen; Lee, Kyung-Bon; Emori, Chihiro et al. (2015) Transcriptomic diversification of developing cumulus and mural granulosa cells in mouse ovarian follicles. Biol Reprod 92:23
Lee, Kyung-Bon; Zhang, Meijia; Sugiura, Koji et al. (2013) Hormonal coordination of natriuretic peptide type C and natriuretic peptide receptor 3 expression in mouse granulosa cells. Biol Reprod 88:42
Zhang, Meijia; Su, You-Qiang; Sugiura, Koji et al. (2011) Estradiol promotes and maintains cumulus cell expression of natriuretic peptide receptor 2 (NPR2) and meiotic arrest in mouse oocytes in vitro. Endocrinology 152:4377-85
Su, You-Qiang; Sugiura, Koji; Li, Qinglei et al. (2010) Mouse oocytes enable LH-induced maturation of the cumulus-oocyte complex via promoting EGF receptor-dependent signaling. Mol Endocrinol 24:1230-9
Zhang, Meijia; Su, You-Qiang; Sugiura, Koji et al. (2010) Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science 330:366-9
Sugiura, Koji; Su, You-Qiang; Li, Qinglei et al. (2010) Estrogen promotes the development of mouse cumulus cells in coordination with oocyte-derived GDF9 and BMP15. Mol Endocrinol 24:2303-14
Su, You-Qiang; Sugiura, Koji; Eppig, John J (2009) Mouse oocyte control of granulosa cell development and function: paracrine regulation of cumulus cell metabolism. Semin Reprod Med 27:32-42
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Su, You-Qiang; Sugiura, Koji; Woo, Yong et al. (2007) Selective degradation of transcripts during meiotic maturation of mouse oocytes. Dev Biol 302:104-17